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Background: ‘ALARM’ is a systematic review of available literature aiming to provide updated information on the prevalence of Human Papillomavirus (HPV) in locally-regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide. Methods: Electronic searches were conducted on clinicaltrials.gov, MEDLINE (via Pubmed), Embase and ASCO/ESMO journals of congresses for interventional studies (IS; phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between 01Jan2010 and 31Dec2020. Criteria for study selection included: availability of HPV prevalence data for patients with LA/RM HNC, patient enrollment from 01Jan2010 onwards, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV-positive (HPV+) over total number of HNC enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate, i.e., sum of all HPV+ patients over sum of all HNC patients enrolled, were assessed. Results: Eighty-one studies (62 IS; 19 NIS) were included in this evidence synthesis, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, the mean (pooled) value was 55.8% (50.7%). The majority of published HPV prevalence data were derived from countries in Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively. Mean (pooled) HPV prevalence in Northern Europe was 31.9% (63.1%), numerically higher than the European average. A “p16-based” assay was the most frequently reported HPV detection methodology (58.0%). Conclusion: Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+, with variation across disease stages and geographic regions. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC. The observed rates underscore the relevance of HPV testing and prophylaxis to the prevention and management of these cancers. PROSPERO Number: CRD42021256876

To investigate possible impact of limited vaccine uptake by the private sector since 2007, a prospective observational study included all children

Aim: To evaluate the potential benefits of introducing universal rotavirus (RV) vaccination in Greece. Methods: A decision analytic model was developed to compare the burden and cost of rotavirus gastroenteritis (RVGE) with and without a universal RV vaccination (88% vaccination coverage) for a cohort of children followed from birth until the age of five. Results: Universal RV vaccination would substantially decrease the RVGE burden on the National Health System by reducing RVGE-related hospitalizations/emergency visits and medical consultations by 83% and 75%, respectively. Total RVGE-related costs was estimated at about 7.6 M€ and would be reduced by 5.9 M€ (−78%) if RV vaccination was introduced. A rapid effect is expected with 76% of cases and 84% of costs avoided would be averted within 2 years postvaccine introduction. The societal benefit would also be significant: total annual number of RVGE cases and parent’s lost work days would be reduced by 67% and 78%, respectively. Including indirect costs, the total disease cost reduction would be 9 M€. Conclusion: Introduction of universal RV vaccination in Greece could offer considerable medical and economic benefits for the National Health System and society. Potential herd immunity would improve results in favour of vaccination.

Rotavirus is the leading cause of acute gastroenteritis among young children worldwide. A prospective multi-center study was conducted (2007-2008) in five Pediatric Hospitals to determine the prevalence, the clinical characteristics, and genotype distribution of rotavirus infection in Greece. Faecal samples were examined for the presence of group A rotavirus antigen by immunochromatography. Rotavirus strains were subjected to G and P genotyping by reverse-transcriptase polymerase chain reaction (PCR) and sequencing. A total of 393 children (216 boys) of median age 23 months, participated in the study. Rotavirus was the cause of acute gastroenteritis in 166 children, 42.3% (CI 95%, 37.4-47.1%) of non-hospitalized and 47.8% (CI 95%, 41.7-53.9%) of hospitalized patients. Rotavirus gastroenteritis occurred between December and April in 78.6% of the cases. Most children with RVG (77.8%) were between 3 months and 3 years old. The mean value of Clark severity score was 12.9 +/- 5.1 for RVG and 10.5 +/- 4.9 for non-RVG (P < 0.01). Genotypes were determined in 117 strains and their distribution was as following: G1P[8], 49%; G2P[4], 31%; G4P[8], 10%; G9P[8], 9%; and G8P[14], 1%. In conclusion, rotavirus is a frequent cause of acute gastroenteritis in Greece. The genotypes circulating are similar with those of other European countries. J Med Virol

Background: The aim of this study was to determine the safety, tolerance and efficacy of linezolid for the treatment of infections from Gram-positive bacteria in immunocompromised children with cancer. Methods: This was a prospective non-comparative unblinded study in the Hematology/Oncology Unit over a two-year period, administering linezolid as monotherapy in children with cancer. Results: Seventeen children received linezolid (30 mg/kgr: 3 i.v. per day). Mean duration of linezolid administration was 12.2 days (range, 6–38 days), while the median age of the evaluable patients was 2.2 years (range, 6 months–11.2 years). Primary diagnosis was acute lymphoblastic leukemia (nine patients), brain tumor (three patients), multi-organ Langerhans cell histiocytosis (two patients), rhabdomyosarcoma, Burkitt's lymphoma and ovarian tumor (one patient each). All patients were in the midst of chemotherapy cycles. Ten out of 17 children had positive blood cultures (methicillin-resistant Staphylococcus aureus, four patients; vancomycin-resistant Enterococcus, three patients; penicillin-resistant Streptococcus pneumoniae, three patients), while seven of the 17 had fever and vancomycin-resistant Enterococcus in stool cultures. All patients were considered clinically cured after the end of the linezolid regimen (100% efficacy). The main adverse events were thrombocytopenia grade 1–3 and anemia grade 2–3 (four and two patients, respectively). Chemotherapy-induced myelotoxicity (six patients) was not worsened during linezolid therapy. No bleeding episodes were presented. Self-limited diarrhea grade 1–2 was presented in four patients (mean duration 2 days). The total adverse event rate was 23.5%; however, there was no premature cessation of linezolid in any patient. Conclusions: Linezolid may be another effective and safe therapy to treat infections from resistant Gram-positive bacteria in immunocompromised children, even in young ages.

Purpose: To investigate adipocytokine secretion, at diagnosis and during chemotherapy in children with the acute lymphoblastic leukemia (ALL). Patients and Methods: Serial measurements (6/patient) of the anti-inflammatory cytokine adiponectin and the proinflammatory adipocytokines leptin and resistin were performed at diagnosis and in nearly the entire period of therapy (up to 21 months), in 9 patients with ALL aged 2 to 7 years (median 4.3 y). Body mass index and leukemic burden were estimated at the same time points and correlated with adipocytokine levels. Nine healthy children matched for age, sex, and body mass index were used as controls. Results: At diagnosis, mean adiponectin levels were low (P

There is a theoretical risk, arising from mathematic models, that a universal varicella vaccination program might lead to an increase in herpes zoster (HZ) incidence. We have searched the Medline database to review HZ epidemiologic data in countries that have had varicella vaccination programs in place for many years, and in countries with either short-term routine varicella vaccination programs or no varicella vaccination programs, to examine whether these programs influence HZ incidence. We have also taken into account factors that may affect HZ epidemiology over time, such as use of the new zoster vaccine. Increases in HZ incidence rates have been observed in many countries that have had no varicella vaccination program in place for the last 20 years. The hypothesis that the decreased exposure of adults to the varicella zoster virus owing to routine varicella vaccination programs might increase HZ incidence has not been consistently proven by current data. The combined routine implementation of varicel...

PURPOSE To investigate the presence of early indicators of the dysmetabolic syndrome (DS) in young survivors with acute lymphoblastic leukemia (ALL) in childhood. PATIENTS AND METHODS We enrolled 80 patients with ALL (50 males, median age 13.9 y, median interval since completion of chemotherapy 6.3 y). Sixty-two patients (group A) received chemotherapy only, whereas 18 patients (group B) received chemotherapy and cranial irradiation (18 Gy). RESULTS Frank obesity [25%; confidence interval (CI) 95%, 16.7%-35.6%], increased blood pressure (21%; CI 95%, 13.6%-31.5%), increased serum triglycerides (21%; CI 95%, 13.6%-31.5%), reduced serum high-density lipoprotein cholesterol (12%; CI 95%, 6.7%-21.7%), increased fasting insulin (8%; CI 95%, 3.2%-15.7%), and osteopenia (71%; CI 95%, 60.5%-80.1%) were detected in groups A and B. Reduced IGF-1 (15%; CI 95%, 8.6%-24.6%) and thyroid hormone abnormalities (11%; CI 95%, 5.8%-20.2%) were detected only in group B. In group B, there was a statistically significant increase in the prevalence of obesity (P=0.024), hyperinsulinemia (P=0.004), and the full DS (22%; CI 95%, 8.6%-45.9% vs. 8%; CI 95%, 3.1%-18.0%; P=0.017) compared with group A. CONCLUSIONS Young survivors of childhood ALL, especially those treated with cranial irradiation, are at risk for obesity, dyslipidemia, insulin resistance, hypertension, and the full DS early after the completion of therapy.

Introduction Rotavirus (RV) infection in neonatal age can be mild or even asymptomatic. Several studies have reported that RV is responsible for 31%-87% of pediatric nosocomial diarrhea and causes gastroenteritis outbreaks in pediatric and neonatal units. Objectives Study clinical characteristics, genotypes and risk factors of RV infection in neonatal age. Methods A prospective study was conducted from April 2009 till April 2013 in the neonatal special care unit of the largest tertiary pediatric hospital of Greece. Fecal samples and epidemiological data were collected from each neonate with gastrointestinal symptoms. RV antigen was detected with a rapid immunochromatography test. RV positive samples were further genotyped with RT PCR and sequencing using specific VP7 and VP4 primers. Results Positive for RV were 126/415 samples (30.4%). Mean age of onset was 18 days. Seventy four cases (58%) were hospital acquired. Seasonality of RV infection did not differ significantly throughout the year with the exception of 4 outbreaks. Genotypes found during the study period were G4P[8] (58.7%), G1P[8] (14.7%), G12P[8] (9.3%), G3P[8] (9.3%), G12P[6] (5.3%), G9P[8] (1.3%) and G2P[4] (1.3%). RV cases presented with: diarrhea (81%), vomiting (26.2%), fever (34.9%), dehydration (28.6%), feeding intolerance (39.7%), weight loss (54%), whilst 19% of cases were asymptomatic. Comparing community with hospital acquired cases differences in clinical manifestations were found. Conclusions Significant incidence of nosocomially transmitted RV infection in neonatal age including asymptomatic illness exists. Genotypes causing nosocomial outbreaks are not different from community strains. Circulating vaccines can be effective in prevention of nosocomial RV infection through herd immunity.

The development of antibodies to factor VIII (FVIII) in severely affected haemophilia A patients is a serious complication associated with increased morbidity and mortality. Bypassing agents are used to treat acute bleeding episodes; however, elimination of the inhibitors can only be achieved with immune tolerance therapy (ITT) in 60-80% of cases. High responding (HR) inhibitors are more likely to respond to ITT if the titre is decreased to

Background: Combined immunodeficiency disorders comprise a heterogeneous group of diseases characterized by both humoral and cell-mediated immunodeficiency. Cutaneous granulomas manifestations in children with combined immunodeficiency are rare. Objective: We report the case of a 6-year-old boy who presented with disseminated cutaneous granulomas and a history of multiple infections. Methods and Results: Laboratory evaluation revealed severe combined immunodeficiency, and deoxyribonucleic acid (DNA) analysis confirmed mutations on a gene of chromosome 19 that encodes an enzyme called Janus kinase 3 (Jak-3). Immunohistochemistry revealed expression of CD8+ in the perivascular lymphocytic infiltrate Conclusion: Disseminated granulomatous lesions in children with a history of frequent infections should prompt the clinician to initiate detailed immunocompetence evaluation as they might prove to be the first manifestation of immunologic impairment.

To evaluate the potential benefits of introducing universal rotavirus (RV) vaccination in Greece.A decision analytic model was developed to compare the burden and cost of rotavirus gastroenteritis (RVGE) with and without a universal RV vaccination (88% vaccination coverage) for a cohort of children followed from birth until the age of five.Universal RV vaccination would substantially decrease the RVGE burden on the National Health System by reducing RVGE-related hospitalizations/emergency visits and medical consultations by 83% and 75%, respectively. Total RVGE-related costs was estimated at about 7.6 M€ and would be reduced by 5.9 M€ (-78%) if RV vaccination was introduced. A rapid effect is expected with 76% of cases and 84% of costs avoided would be averted within 2 years postvaccine introduction. The societal benefit would also be significant: total annual number of RVGE cases and parent's lost work days would be reduced by 67% and 78%, respectively. Including indirect costs, the total disease cost reduction would be 9 M€.Introduction of universal RV vaccination in Greece could offer considerable medical and economic benefits for the National Health System and society. Potential herd immunity would improve results in favour of vaccination.

The aim of this study was to determine the safety, tolerance and efficacy of linezolid for the treatment of infections from Gram-positive bacteria in immunocompromised children with cancer.This was a prospective non-comparative unblinded study in the Hematology/Oncology Unit over a two-year period, administering linezolid as monotherapy in children with cancer.Seventeen children received linezolid (30 mg/kgr: 3 i.v. per day). Mean duration of linezolid administration was 12.2 days (range, 6-38 days), while the median age of the evaluable patients was 2.2 years (range, 6 months-11.2 years). Primary diagnosis was acute lymphoblastic leukemia (nine patients), brain tumor (three patients), multi-organ Langerhans cell histiocytosis (two patients), rhabdomyosarcoma, Burkitt's lymphoma and ovarian tumor (one patient each). All patients were in the midst of chemotherapy cycles. Ten out of 17 children had positive blood cultures (methicillin-resistant Staphylococcus aureus, four patients; vancomycin-resistant Enterococcus, three patients; penicillin-resistant Streptococcus pneumoniae, three patients), while seven of the 17 had fever and vancomycin-resistant Enterococcus in stool cultures. All patients were considered clinically cured after the end of the linezolid regimen (100% efficacy). The main adverse events were thrombocytopenia grade 1-3 and anemia grade 2-3 (four and two patients, respectively). Chemotherapy-induced myelotoxicity (six patients) was not worsened during linezolid therapy. No bleeding episodes were presented. Self-limited diarrhea grade 1-2 was presented in four patients (mean duration 2 days). The total adverse event rate was 23.5%; however, there was no premature cessation of linezolid in any patient.Linezolid may be another effective and safe therapy to treat infections from resistant Gram-positive bacteria in immunocompromised children, even in young ages.

PURPOSE To investigate peptide YY (PYY) and ghrelin secretion, at diagnosis and during chemotherapy in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Measurements were performed at diagnosis, after the induction-consolidation phase and at standard time points before each cycle in 9 patients with ALL aged 2 to 7 years (median 4.3 y). Body mass index (BMI) and leukemic burden were estimated at the same time points and correlated with PYY and ghrelin levels. Nine healthy children matched for age and sex were used as controls. RESULTS At diagnosis, mean PYY levels were high (P

Two patients, a 4-year-old boy and a 6-year-old girl who had a 2-year and a 3-year history of idiopathic thrombocytopenic purpura, respectively, were referred to our Department. Both patients had frequent haemorrhagic events. They received i.v. immunoglobulin, corticosteroids, cyclosporine, interferon alpha-2b and azathioprine, but no clinical remission was established. The girl also underwent splenectomy. Anti-CD20 antibody was administered to both patients at a dose of 375 mg/m(2) once weekly for 4 weeks. No side-effects were detected. During the 18-month follow-up period the patients received no other drug and remained in clinical remission. The B lymphocytes remained undetectable in peripheral blood for 3 months and they progressively increased during the following 4 months. Rituximab is a novel, quite effective, safe treatment of chronic refractory idiopathic thrombocytopenic purpura in childhood. More studies and follow up of patients for longer periods are necessary.

Epidemiologic studies have indicated a relationship between serum lipids and cancer, and it is possible that lipid abnormalities are involved in the mechanism of oncogenesis. This study was performed to investigate serum lipid alterations in patients with acute lymphoblastic leukemia (ALL) at diagnosis and during remission of the disease. Plasma lipids and lipoproteins were measured at diagnosis, prior to the administration of induction treatment, and every 2 months for the first 12 months of the maintenance phase of chemotherapy in 64 patients with ALL. Nearly all patients demonstrated a predictable pattern of serum lipid alterations that consisted of extremely low levels of high-density lipoprotein cholesterol, elevated triglycerides, and elevated low-density lipoprotein cholesterol. Patients studied again during remission demonstrated a return to normal values, and the difference was statistically significant. The results suggest that at diagnosis of ALL an abnormality in lipid metabolism is present, which is reversed during remission.

A 12-year-old girl with chronic otitis media complicated by petrositis and cerebellar abscess is presented. Early surgical intervention, in combination with broad-spectrum antibiotics, provided a good outcome. Life-threatening complications of otitis media, although rare, still occur in developed countries.

We present the results of a prospective multi-center, community-based epidemiological observational study regarding the clinical burden of pediatric rotavirus gastroenteritis (PRG) in Greece.

INTRODUCTION: Pediatric rotavirus gastroenteritis (PRG) is the most frequent cause of severe acute gastroenteritis (AGE) in children up to 5 years of age worldwide. OBJECTIVE: We sought to determine the proportion of PRG and compare its clinical burden to that of AGE caused by other pathogens. METHODS: The study was conducted in 4 hospital emergency units (HEUs) and 50 private pediatric clinics between January and May 2006. Children up to 5 years of age were included. A rapid stool immunochromatographic test for rotavirus antigen detection was performed. Symptom-severity scores were calculated by using the Clark scale. RESULTS: Seven hundred and six children participated in the study (median age: 20 months; 385 boys [54.5%]); 273 patients (38.6%) visited HEUs, and 433 (61.4%) visited private clinics. The proportion of PRG was 29% (95% confidence interval [CI]: 25.9%–32.6%) in the total study group, 18.3% (95% CI: 14.9%–22.3%) in private clinics, 45.7% (95% CI: 40.0%–51.7%) in HEUs, and 49.1% in hospitalized patients (95% CI: 42.3%–55.7%). Most children with PRG (71.7%) were between 6 months and 3 years old. Behavioral changes and signs of dehydration, weight loss, fever at ≥38°C, diarrhea, and vomiting were more prevalent with PRG (P < .01). In children with PRG, a higher incidence of moderate or severe gastroenteritis (P = .013 and .021, respectively), hospitalization (P = .011), and need for a clinical reevaluation (P = .012) was observed, as was longer hospitalization (5.14 ± 3.18 vs 3.69 ± 2.25 days; P = .039). CONCLUSIONS: PRG was responsible for nearly half the patients with AGE who visited HEUs or required hospitalization. Vaccination against rotavirus would help prevent this frequent and often severe disease.

An increased incidence of obesity and cardiovascular morbidity and mortality was recently observed in adult survivors of childhood malignancies younger than 45 years. The purpose of this study was to investigate the presence of early indicators of the dysmetabolic syndrome in a population of young survivors of acute lymphoblastic leukemia (ALL) in childhood. Patients and methods: Our study included 58 patients (31 males), aged 5–24 years (mean 12.9 years) with ALL, who had finished their treatment by the same protocol at least 2 years before the study (mean 5.1 years, range 2–10 years). Ten patients had received cranial irradiation (18 Gy). No patient had a history of thyroid disease or diabetes mellitus or received hormonal substitution. We obtained a detailed history of their diet habits and level of physical activity and measured their body mass index (BMI) and blood pressure (BP). Complete blood counts and blood chemistry tests were also obtained. Finally, bone density was measured in the lumbar spine and femur with DEXA. Results: Diet enriched in lipids and low carbohydrates was reported by 43/58 (74%), while absence of any athletic activity by 38/58 (65%) of the patients. Frank obesity with a BMI >30 or its equivalent for age and gender was observed in 12/58 (21%) of the patients, while 25/58 (43%) were overweight, with a BMI >2595th percentile) was observed in 13/58 patients (22%), while in 25/58 (43%) it was > the 75th percentile. Dyslipidemia characterized by one, two, or three indices (serum cholesterol, triglycerides or LDL concentrations >95th percentile) was respectively detected in 20/58 (35%), 13/58 (22%), and 7/58 (12%) of the patients. Reduced serum HDL concentrations ( Conclusion: Survivors of childhood ALL have early indicators of high risk for the dysmetabolic syndrome. Modification of diet, body weight control, stress reduction, and reinforcement of an exercise program will hopefully be helpful in preventing the cardiovascular sequelae of the syndrome, improve the quality of life and enhance the life expectancy in this group of patients.

Anti-CD20, a chimeric monoclonal antibody (rituximab), binds avidly to the CD20 antigen, which is expressed almost exclusively on the surface of B-cells in different stages of their development. The observed elimination of B cells from serum and lymphoid tissue of patients treated with anti-CD20 suggests that this agent could have a beneficial effect in immune diseases such as chronic immune thrombocytopenic purpura (cITP), autoimmune hemolytic anemia or hemophilia with inhibitors. Anti-CD20 was given to two children with refractory cITP and another two with hemophilia and FVIII inhibitors. All 4 children had frequent admissions to the hospital and poor quality of life. Anti-CD20 was administered at a dose of 375mg/m2, once weekly, for 4 consecutive weeks. B cells were measured in peripheral blood with monoclonal antibodies CD19 and CD20, before induction of treatment and in certain time-points after drug administration. Case 1: A 5 2/12-year old girl with cITP, diagnosed at the age of 2 3/12, presented with profound thrombocytopenia and recurrent hemorrhages from several systems, including CNS. She was refractory to any available therapy, therefore an unsuccessful splenectomy was performed at the age of 3 6/12. Following splenectomy, she continued to be severely thrombocytopenic and symptomatic, not responding even to immunosuppressive agents. Patient received anti-CD20, three years from the onset of the disease. Case 2: A 7 4/12 -year old boy was diagnosed as having ITP at the age of 5 9/12. Due to frequent bleedings, not responsive to the available therapy plus azathioprime, he was administered anti-CD20 to postpone splenectomy. Case 3 and 4: Two severely affected hemophiliacs (F VIII Results: Both cITP patients initially increased their platelet values to 90′109/L and 40′109/L respectively for the first three months. 17 and 9 months from the initiation of the rituximab, children were asymptomatic, although they presented with fluctuations of the platelet values (10–30′109/L). Both hemophiliacs reduced their inhibitor titer to 4.8 BU and 4.0 BU respectively, therefore ITT was applied. Case 3, lost the antibody within 21 days and he has been on successful prophylactic therapy for the last 6 months. Case 4 had an initial increase in titer, followed by a decline. Despite the frank reduction of CD-19 and CD-20 B-cells, none of the patients suffered any infection. Conclusion: Anti-CD20 seems to be an optional therapeutic tool for children with refractory cITP or hemophiliacs with high titer inhibitors, in case ITT has to be applied. Although patients may have a poor laboratory response, they acquire a better quality of life minimizing hospital admissions. However, long-term complications have to be studied in a larger scale.